SUMMARY More than 300,000 babies are born annually with sickle cell disease (SCD), 90% of which occur in developing countries, with the largest number in Nigeria. A majority of children with SCD die before 5 years, but when early SCD screening is coupled with health care management, mortality can be reduced dramatically. Unfortunately, because universal screening requires blood samples from infants, it is rarely done in resource-limited settings where it is expensive and hard to implement. A simple, economical and portable point-of-care (POC) screening test that is well accepted by families, avoids the need for blood sampling, and is easily integrated into the existing community health care system without diverting time and resources from other healthcare priorities is critically needed. To this end, Capnia has modified the portable CoSense End Tidal Carbon Monoxide (ETCO) Monitor to make it suitable for point of care use as a SCD screening tool in tropical climates. The monitor non-invasively measures carbon monoxide in breath, a byproduct of hemolysis, and clearly distinguishes between children with or without SCD. Because measurements can be made without a forced breath sample, it is suitable for use in infants and young children who cannot reliably follow sample collection commands. Further, the only disposable item required is an inexpensive nasal cannula. Thus, this simple-to-use device meets all of the desirable characteristics for use as a SCD screening tool in low resource settings. In order to fully prepare the device and develop an SCD screening regimen for commercial deployment we propose four aims. In Aim 1 we will determine the optimal age at which infants should be screened using ETCO and a recommended ETCO threshold at which they should be referred for further SCD. We will also define the sensitivity and specificity of detecting SCD in Nigerian children. In Aim 2 we will enhance the usability of CoSense-S to make it suitable for field use in Nigeria and develop training materials to support its commercial deployment for SCD screening. Work in Aim 3 will test the reliability and ease of use of CoSense-S in field conditions in Nigeria. Our goal is to test and validate the modified monitor, CoSense-S, for SCD screening in the field in Nigeria. If successful, we will be ready to commercialize a device that will for the first time make widespread screening for SCD feasible in low resource settings.